Lawrence Hayward

Summary

Affiliation: University of Massachusetts Medical School
Country: USA

Publications

  1. ncbi request reprint Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 277:15923-31. 2002
  2. pmc Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 118:1437-49. 2008
  3. ncbi request reprint Familial amyotrophic lateral sclerosis mutants of copper/zinc superoxide dismutase are susceptible to disulfide reduction
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 278:5984-92. 2003
  4. pmc Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules
    Daryl A Bosco
    Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Hum Mol Genet 19:4160-75. 2010
  5. ncbi request reprint Inhibition of chaperone activity is a shared property of several Cu,Zn-superoxide dismutase mutants that cause amyotrophic lateral sclerosis
    Hemachand Tummala
    Department of Biochemistry and Molecular Pharmacology, Neurology, and Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 280:17725-31. 2005
  6. pmc Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 284:27746-58. 2009
  7. ncbi request reprint Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Biol Chem 280:29771-9. 2005
  8. ncbi request reprint Mutant SOD1 instability: implications for toxicity in amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
    Neurodegener Dis 2:115-27. 2005
  9. ncbi request reprint Familial amyotrophic lateral sclerosis-associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutase
    Jorge A Rodriguez
    Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095 1569, USA
    J Biol Chem 277:15932-7. 2002
  10. pmc Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis
    Xiaohang Cao
    Department of Biochemistry and the X ray Crystallography Core Laboratory, The University of Texas Health Ssience Center, San Antonio, Texas 78229, USA
    J Biol Chem 283:16169-77. 2008

Research Grants

  1. Role of SOD Instability in ALS Motor Neuron Toxicity
    Lawrence Hayward; Fiscal Year: 2006

Collaborators

Detail Information

Publications21

  1. ncbi request reprint Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 277:15923-31. 2002
    ..Further characterization of these as-isolated SOD1 proteins may provide new insights regarding mutant SOD1 enzyme toxicity in ALS...
  2. pmc Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 118:1437-49. 2008
    ....
  3. ncbi request reprint Familial amyotrophic lateral sclerosis mutants of copper/zinc superoxide dismutase are susceptible to disulfide reduction
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 278:5984-92. 2003
    ..These results implicate SOD1 destabilization under cellular disulfide-reducing conditions at physiological pH and temperature as a shared property that may be relevant to amyotrophic lateral sclerosis mutant neurotoxicity...
  4. pmc Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules
    Daryl A Bosco
    Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Hum Mol Genet 19:4160-75. 2010
    ..These findings demonstrate a potential link between FUS mutations and cellular pathways involved in stress responses that may be relevant to altered motor neuron homeostasis in ALS...
  5. ncbi request reprint Inhibition of chaperone activity is a shared property of several Cu,Zn-superoxide dismutase mutants that cause amyotrophic lateral sclerosis
    Hemachand Tummala
    Department of Biochemistry and Molecular Pharmacology, Neurology, and Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 280:17725-31. 2005
    ..Thus, mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of ALS-linked mutant SOD1 proteins...
  6. pmc Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 284:27746-58. 2009
    ..Overall, our findings support the notion that misfolding associated with metal deficiency may facilitate aberrant interactions of SOD1 with itself or with other cellular constituents and may thereby contribute to neuronal toxicity...
  7. ncbi request reprint Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Biol Chem 280:29771-9. 2005
    ..These abnormally hydrophobic SOD1 species may promote aberrant interactions of the enzyme with itself or with other cellular constituents to produce toxicity in familial ALS...
  8. ncbi request reprint Mutant SOD1 instability: implications for toxicity in amyotrophic lateral sclerosis
    Ashutosh Tiwari
    Department of Neurology, University of Massachusetts Medical School, Worcester, 01655, USA
    Neurodegener Dis 2:115-27. 2005
    ..The challenge for future investigations is to relate these abnormal properties of partially unfolded SOD1 to specific mechanisms of toxicity in motor neurons, supporting cells, or target tissues...
  9. ncbi request reprint Familial amyotrophic lateral sclerosis-associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutase
    Jorge A Rodriguez
    Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095 1569, USA
    J Biol Chem 277:15932-7. 2002
    ..We conclude that decreased conformational stability shared by all of these mutant SOD1s may contribute to SOD1 toxicity in FALS...
  10. pmc Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis
    Xiaohang Cao
    Department of Biochemistry and the X ray Crystallography Core Laboratory, The University of Texas Health Ssience Center, San Antonio, Texas 78229, USA
    J Biol Chem 283:16169-77. 2008
    ..These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis...
  11. ncbi request reprint The structure of holo and metal-deficient wild-type human Cu, Zn superoxide dismutase and its relevance to familial amyotrophic lateral sclerosis
    Richard W Strange
    Molecular Biophysics Group, Department of Synchrotron Radiation, CCLRC Daresbury Laboratory, Warrington, Cheshire, UK
    J Mol Biol 328:877-91. 2003
    ....
  12. doi request reprint Retrograde axonal transport and motor neuron disease
    Anna Lena Strom
    Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
    J Neurochem 106:495-505. 2008
    ..We further consider how the interference with axonal transport and protein turnover by mutant SOD1 could influence the function and viability of motor neurons in ALS...
  13. pmc Interaction of amyotrophic lateral sclerosis (ALS)-related mutant copper-zinc superoxide dismutase with the dynein-dynactin complex contributes to inclusion formation
    Anna Lena Strom
    Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536, USA
    J Biol Chem 283:22795-805. 2008
    ..Whether the misfolded SOD1s directly perturb axonal transport or impair other functional properties of the dynein motor, this interaction could propagate a toxic effect that ultimately causes motor neuron death in ALS...
  14. pmc Detergent-insoluble aggregates associated with amyotrophic lateral sclerosis in transgenic mice contain primarily full-length, unmodified superoxide dismutase-1
    Bryan F Shaw
    Department of Chemistry and Biochemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
    J Biol Chem 283:8340-50. 2008
    ..The results demonstrate that the principal protein in the high molecular mass aggregates whose appearance correlates with symptoms of the disease is the unmodified, full-length SOD1 polypeptide...
  15. ncbi request reprint Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis
    Shohei Watanabe
    Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
    Free Radic Biol Med 42:1534-42. 2007
    ..Aberrant Cu binding at the Cys111 residue may be a significant factor in altering mutant SOD1 behavior and may explain the benefit of controlling Cu access to mutant SOD1 in models of familial ALS...
  16. pmc Destabilization of apoprotein is insufficient to explain Cu,Zn-superoxide dismutase-linked ALS pathogenesis
    Jorge A Rodriguez
    Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 102:10516-21. 2005
    ..Thus, the ALS mutant Cu,Zn-superoxide dismutase apoproteins do not all share reduced global stability, and additional properties must be identified and understood to explain the toxicity of all of the mutant proteins...
  17. ncbi request reprint Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS
    Jennifer Stine Elam
    Department of Biochemistry and the Center for Biomolecular Structure Analysis, The University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229 3900, USA
    Nat Struct Biol 10:461-7. 2003
    ..Loss of this protection through conformational rearrangement in the metal-deficient enzyme could be a toxic property common to mutants of SOD1 linked to FALS...
  18. ncbi request reprint An alternative mechanism of bicarbonate-mediated peroxidation by copper-zinc superoxide dismutase: rates enhanced via proposed enzyme-associated peroxycarbonate intermediate
    Jennifer Stine Elam
    Department of Biochemistry and the X ray Crystallography Core Laboratory, University of Texas Health Science Center, San Antonio, Texas 78229 3900, USA
    J Biol Chem 278:21032-9. 2003
    ..The orientation of the enzyme-associated oxyanion suggests that both the self-oxidative and external oxidative pathways can proceed through an enzyme-associated peroxycarbonate intermediate...
  19. pmc Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg
    Svetlana Antonyuk
    Molecular Biophysics Group, CCLRC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD, UK
    Protein Sci 14:1201-13. 2005
    ....
  20. pmc Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutants
    Michael A Hough
    Molecular Biophysics Group, Council for the Central Laboratory of the Research Councils, Daresbury Laboratory, Warrington, Cheshire WA4 4AD, United Kingdom
    Proc Natl Acad Sci U S A 101:5976-81. 2004
    ....
  21. ncbi request reprint Interaction between familial amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants and the dynein complex
    Fujian Zhang
    Graduate Center for Nutritional Sciences, Department of Molecular and Cellular Biochemistry, College of Medicine, Lexington, Kentucky 40536, USA
    J Biol Chem 282:16691-9. 2007
    ..The aberrant interaction is potentially critical to the formation of mutant SOD1 aggregates as well as the toxic cascades leading to motor neuron degeneration in ALS...

Research Grants5

  1. Role of SOD Instability in ALS Motor Neuron Toxicity
    Lawrence Hayward; Fiscal Year: 2006
    ..Future results from Aims 1 and 2 may favor alternative hypotheses of mutant SOD1 toxicity to test in these cellular models and may suggest new therapeutic approaches to evaluate in ALS mice. ..